Biomarkers for risk stratification of patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: Insights from the Platelet Inhibition and Patient Outcomes trial

Velders, Matthijs A.; Wallentin, Lars; Becker, Richard C.; Boven, A.J. van; Himmelmänn, Anders; Husted, Steen; Katus, Hugo A.; Lindholm, Daniel; Morais, João; Siegbahn, Agneta; Storey, Robert F.; Wernroth, Lisa; James, Stefan

doi:10.1016/j.ahj.2015.02.019

Cited by 42 publications

(47 citation statements)

References 32 publications

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“…GDF‐15 was measured with a precommercial assay (Roche Diagnostics) using a monoclonal mouse antibody for capture and a monoclonal mouse antibody fragment for detection in a sandwich assay format. The results of these analyses in relation to outcomes and effects of study treatment have previously been reported 8, 9, 10…”

Section: Methodsmentioning

confidence: 91%

“…Several biomarkers, on admission for ACS, provide clinically important information on risk for cardiovascular morbidity and mortality, including NT‐proBNP (myocardial dysfunction),9, 10 cardiac troponins (myocardial necrosis),29 and cystatin C (kidney function) 7, 11. Circulating osteoprotegerin has been reported to be associated with cardiovascular outcomes, including mortality, MI, and incident heart failure, in several ACS cohorts 16, 17, 18, 19.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating osteoprotegerin has been reported to be associated with cardiovascular outcomes, including mortality, MI, and incident heart failure, in several ACS cohorts 16, 17, 18, 19. However, although most of these studies include natriuretic peptides,16, 17, 19 troponins,16, 17, 18 and CRP16, 17, 18 in their adjustment strategy, none include GDF‐15, which increases in response to myocardial stress associated with inflammation and tissue damage30 and is becoming a recognized biomarker in ACS 9, 10, 14. In this large study population, the association between high osteoprotegerin levels at admission and risk of the primary end point or cardiovascular death was markedly attenuated and no longer significant after addition of NT‐proBNP, hs‐TnT, and GDF‐15 to the model that included clinical variables and inflammatory biomarkers.…”

Section: Discussionmentioning

confidence: 99%

“…Circulating biomarkers provide independent information on risk for adverse outcomes on top of established demographic and clinical variables in patients with acute coronary syndromes (ACSs) 7, 8, 9, 10, 11. In addition to the established natriuretic peptides and cardiac troponins, which have been extensively evaluated and shown to be suitable biomarkers for prognosis and/or risk stratification of ACS,12, 13 the recently characterized inflammatory marker, growth differentiation factor‐15 (GDF‐15), may also provide additional clinically useful prognostic information in ACS 14.…”

mentioning

confidence: 99%

“…Also, cystatin C, a marker of kidney function, has recently gained increasing relevance as an independent marker of mortality in ACS 15. Accordingly, we have recently shown that NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide),9, 10 high‐sensitivity troponin T (hs‐TnT),9, 10 GDF‐15,8, 9, 10 and cystatin C7 display independent associations with cardiovascular outcomes, including cardiovascular death, in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Therefore, they represent important adjustment variables for evaluating the independent contribution of new biomarkers to prognosis.…”

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confidence: 99%

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Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Ueland

Åkerblom

Ghukasyan

et al. 2018

JAHA

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BackgroundElevated levels of osteoprotegerin, a secreted tumor necrosis factor–related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial.Methods and ResultsThe associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non–coronary artery bypass grafting major bleeding during 1 year of follow‐up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21–1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C‐reactive protein, troponin T, NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], and growth differentiation factor‐15). The corresponding rates of non–coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36–1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09–1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89–1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91–1.96).ConclusionsIn patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

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Section: Methodsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Ueland

Åkerblom

Ghukasyan

et al. 2018

JAHA

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Growth differentiation factor‐15 and the risk of cardiovascular diseases and all‐cause mortality: A meta‐analysis of prospective studies

Xie

Liu

2019

Clinical Cardiology

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Background and Aim Previous studies have documented that the association between growth differentiation factor‐15 (GDF‐15) the risk of patients with cardiovascular diseases (CVDs). In this meta‐analysis, our main objective is to explore the associations between GDF‐15 and the risk of CVD or all‐cause mortality. Methods PubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard ratio (HR) with 95% confidence interval (CI), with regard to the association between GDF‐15 levels and subsequent risk of CVDs or all‐cause mortality. A random‐effect model was applied to pool the HR and 95% CI. Results Thirty‐one prospective studies met the eligibility criteria involving 53 706 subjects with 7020 adverse outcome events. It was concluded that GDF‐15 levels were associated with an incremental risk of CVDs or all‐cause mortality. Highest GDF‐15 category was associated with greater risk of cardiovascular mortality (HR, 2.66; 95% CI, 1.69‐3.63), all‐cause mortality (HR, 2.52; 95% CI, 2.06‐2.97), and complex adverse outcome (HR, 1.81; 95% CI, 1.42‐2.21). As each log‐unit increment in GDF‐15 concentration, the corresponding risk of adverse events also escalated, cardiovascular mortality (HR, 2.11; 95% CI, 1.57‐2.66), all‐cause mortality (HR, 2.70; 95% CI, 2.29‐3.12), and complex adverse outcome (HR, 1.96; 95% CI, 1.64‐2.29). Conclusions Judging from the results of the data analysis, GDF‐15 levels may increase the risk of CVDs or all‐cause mortality.

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Interleukin‐18 in patients with acute coronary syndromes

Åkerblom

James

Lakic

et al. 2019

Clinical Cardiology

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BackgroundWe aimed to assess associations between circulating IL‐18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).Hypothesis and MethodsPlasma IL‐18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT‐hs, NT‐proBNP, cystatin C, CRP‐hs, and GDF‐15).ResultsMedian IL‐18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF‐15, and CRP‐hs were independently associated with higher IL‐18 levels. Higher baseline IL‐18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02‐1.07 and HR 1.10, 95% CI 1.06‐1.14, respectively, per 25% increase of IL‐18 levels). Associations remained significant after adjustment for clinical variables but became non‐significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98‐1.04 and HR 1.04, 95% CI 1.00‐1.08, respectively). There were no associations with sMI.ConclusionsIn ACS patients, IL‐18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL‐18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.

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Biomarkers for risk stratification of patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: Insights from the Platelet Inhibition and Patient Outcomes trial

Abstract: Biomarker measurement on admission is feasible and provides incremental risk stratification in patients with STEMI treated with PPCI, with NT-proBNP and GDF-15 being most valuable due to the association with both CVD and spontaneous MI.

Cited by 42 publications

References 32 publications

Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial

Growth differentiation factor‐15 and the risk of cardiovascular diseases and all‐cause mortality: A meta‐analysis of prospective studies

Interleukin‐18 in patients with acute coronary syndromes

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